Dataset Information

The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.

ABSTRACT: Our work explores the relationship between G protein-coupled receptor kinase-5 (GRK5) single nucleotide polymorphisms and Alzheimer's disease risk. We confirmed that GRK5 translocates from the cellular membrane to the cytosol in the hippocampus of Alzheimer's disease mice and that GRK5 deficiency promotes tau hyperphosphorylation, a hallmark of Alzheimer's disease pathology. Our results indicate that one functional variant, or mutant, of GRK5 (GRK5-Gln41Leu) decreased GRK5 translocation from the membrane to the cytoplasm and reduced tau hyperphosphorylation, whereas, another GRK5 mutant (GRK5-Arg304His) increased GRK5 translocation to the cytoplasm and promoted tau hyperphosphorylation. In addition, case-control studies revealed that GRK5-Gln41Leu is associated with a lower risk of late-onset Alzheimer's disease. Our findings suggest that the GRK5-Gln41Leu mutant may resist tau hyperphosphorylation by promoting GRK5 membrane stability and, in effect, may contribute to lower Alzheimer's disease risk.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5641163 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.

Zhang Yuan Y Zhao Jianghao J Yin Mingkang M Cai Yujie Y Liu Shengyuan S Wang Yan Y Zhang Xingliang X Cao Hao H Chen Ting T Huang Pengru P Mai Hui H Liu Zhou Z Tao Hua H Zhao Bin B Cui Lili L

Oncotarget 20170816 42

Our work explores the relationship between G protein-coupled receptor kinase-5 (GRK5) single nucleotide polymorphisms and Alzheimer's disease risk. We confirmed that GRK5 translocates from the cellular membrane to the cytosol in the hippocampus of Alzheimer's disease mice and that GRK5 deficiency promotes tau hyperphosphorylation, a hallmark of Alzheimer's disease pathology. Our results indicate that one functional variant, or mutant, of GRK5 (GRK5-Gln41Leu) decreased GRK5 translocation from the ...[more]

PMID: 29069820

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Dataset Information

The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.

Publications

The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.

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